This proposal is a study of regulatory systems in vascular muscle associated with the coupling of stimulus to vascular response. It is concerned with how experimental hypertension impinges on and alters vascular muscle intracellular regulatory systems. It looks for changes resulting from the hypertension models under study which may escalate the hypertension or alter vascular muscular permeability of changes when the hypertensive process is reversed. The systems selected for study include intracellular calcium sequestration, the calcium dependent regulatory protein (CDR), which may transduce the calcium signal for contraction, and membrane phospholipid methylation which relates to fluidity of membrane and possibly to agonist sensitivity. The study visualizes as critically important: a) a functional calcium pool in the sarcoplasmic reticulum, b) activity of calcium transducer (CDR protein) on regulatory systems of vascular muscle, and c) phospholipid methylation as a possible factor in responsiveness to critical agonists. The experimental work proposed includes the measurement in normotensive and hypertensive vessels of calcium uptake in microsomes and microsomal subfractions, pharmacologic assessment of intracellular calcium pool function, CDR protein membrane interaction in vascular muscle, CDR effects of vascular muscle calcium regulation, phospholipid methylation activity and effects on methyl group precursor on the vascular response.